One postulate to explain the decrement of performance in aged organisms is that proteins and other macromolecules and organelles containing biosynthetic or post-synthetic errors are accumulated in older cells and interfere with their efficacy of function. This population of error proteins we have sought for in rat, mouse and dog tissues and despite earlier reports in the literature we have failed to find evidence of a significantly decreased level of specific activity in aldolase and superoxidase dismutase. The possibility remains that there is a significant population of proteins not readily discriminated by our technique and one reason for their presence could be the decreased efficacy of protein catabolism in old cells. We have therefore undertaken an examination of the catabolic rate of intact and variously modified protein in the perfused liver system using rats and mice of known ages. These experiments have demonstrated the dependence of the uptake and catabolism in this system upon various states of modification of the protein and we will pursue these investigations using various methods of modifying the proteins and we will explore additional ways of delivering the proteins to the liver cells (i.e., in liposomes or bound to isolated organelles and dead bacteria) in order to differentiate the processes of assimilation or phagocytosis or pinocytosis and catabolism. Previous studies on the rate of virus production in old and young cells has shown little difference implying that the protein synthetic mechanisms in old cells are not notably deficient; these studies should indicate whether or not the catabolic mechanisms of the cells deteriorate with age.